Translocational inefficiency of intracellular proteins in senescence of human diploid fibroblasts.
Ann N Y Acad Sci
; 928: 176-81, 2001 Apr.
Article
in En
| MEDLINE
| ID: mdl-11795508
ABSTRACT
In order to investigate signal transduction pathways and related changes of actin cytoskeleton organization in cellular senescence, H-ras double mutants--V12S35, V12G37, and V12C40--were constitutively expressed in human foreskin fibroblast (HDF). Senescent HDF cells as well as the H-ras mutant expressers accumulated p-Erk1/2 in the cytoplasm with increased MEK activity and failed to translocate it to nuclei on EGF stimulation. Senescent HDF cells, V12S35 and V12G37 expressers, revealed a failure to export actin fiber from nucleus to cytoplasm and also to form stress fibers. Perinuclear expression of Rac1 was prominent in the HDF cells and V12C40 expresser; however, in the V12S35 expresser, translocation of Rac1 from perinucleus to nucleus and strong expression of RhoA were obvious. In summary, the H-ras double mutant expressers induced premature senescence through the MEK pathway, accompanied by nuclear accumulation of actin and Rac1 proteins, cytoplasmic retention of p-Erk1/2, and marked induction of RhoA expression, suggesting the translocational inefficiency of the intracellular proteins in the senescent HDF cells.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytoskeleton
/
Genes, ras
/
Cellular Senescence
/
MAP Kinase Signaling System
/
Active Transport, Cell Nucleus
/
MAP Kinase Kinase Kinase 1
/
Fibroblasts
Language:
En
Journal:
Ann N Y Acad Sci
Year:
2001
Document type:
Article